chr21-44852737-T-C

Position:

• chr21-44852737-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004339.4(PTTG1IP):​c.497-1110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,862 control chromosomes in the GnomAD database, including 3,120 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3120 hom., cov: 32)
• Consequence: PTTG1IP NM_004339.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

PTTG1IP (HGNC:13524): (PTTG1 interacting protein) This gene encodes a single-pass type I integral membrane protein, which binds to pituitary tumor-transforming 1 protein (PTTG1), and facilitates translocation of PTTG1 into the nucleus. Coexpression of this protein and PTTG1 induces transcriptional activation of basic fibroblast growth factor. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTTG1IP	NM_004339.4	c.497-1110A>G		intron_variant		ENST00000330938.8	NP_004330.1
PTTG1IP	NM_001286822.2	c.169-1110A>G		intron_variant			NP_001273751.1
PTTG1IP	NR_104597.2	n.462-1110A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTTG1IP	ENST00000330938.8	c.497-1110A>G		intron_variant		1	NM_004339.4	ENSP00000328325	P1
PTTG1IP	ENST00000397886.3	c.434-1110A>G		intron_variant		4		ENSP00000380983
PTTG1IP	ENST00000397887.7	c.278-1110A>G		intron_variant		4		ENSP00000380984
PTTG1IP	ENST00000445724.3	c.169-1110A>G		intron_variant		2		ENSP00000395374

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27411 AN: 151744 Hom.: 3117 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27419 AN: 151862 Hom.: 3120 Cov.: 32 AF XY: 0.182 AC XY: 13493 AN XY: 74216

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.182

Alfa AF: 0.229 Hom.: 2115

Bravo AF: 0.166

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1344110; hg19: chr21-46272652;